Biomarkers and their association with cognitive impairment in patients with chronic heart failure: a systematic review and meta-analysis

Introduction: The aim was to synthesize the evidence on the association between circulating biomarkers and Cognitive Impairment (CI) in patients with Chronic Heart Failure (CHF), and to assess methodological quality and certainty of evidence.Methods: Systematic review and meta-analysis conducted under PRISMA 2020 (PROSPERO CRD42024626152). Searches were performed in PubMed/MEDLINE, Scopus, Web of Science, and Embase up to April 30, 2025. Observational studies and clinical trials that measured cardiac or extracardiac biomarkers in patients with HF and evaluated CI using validated tools were included. Mean differences (MD) were calculated using random-effects models (DerSimonian–Laird). Methodological quality was assessed with the Newcastle-Ottawa Scale (NOS) and certainty of evidence with the GRADE approach.Results: Seven studies met the inclusion criteria. Patients with CHF and CI had significantly higher levels of highsensitivity troponin T (hs-cTnT) compared to those without CI (MD 3.36 ng/L; 95% CI 0.42-6.31; p = 0.03; I² = 0%). In contrast, NT-proBNP showed a non-significant trend (MD 410.16 pg/mL; 95% CI −276.22-1096.53; p = 0.24; I² = 51%). Methodological quality was moderate (median NOS 7/9). Extracardiac biomarkers such as GDF-15, S100B, pTau, NfL, BDNF, and sICAM-1/sVCAM-1 were associated with inflammation, endothelial dysfunction, and neurodegeneration. With GRADE, overall certainty was very low for both biomarkers due to observational design, imprecision, and heterogeneity.Conclusions: hs-cTnT is consistently associated with CI in HF, whereas NT-proBNP does not show a robust relationship. Extracardiac biomarkers may provide complementary information in cognitive stratification, although their clinical application requires validation in multicenter longitudinal cohorts with analytical and neuropsychological standardization.